International Scholarly Research Notices

Review Article

The Modern Primitives: Applying New Technological Approaches to Explore the Biology of the Earliest Red Blood Cells

Table 1

Genes critical in primitive erythropoiesis as demonstrated by null mutation.


Gene	EryP phenotype of null mutant embryos

Klf1/Eklf	EryP show abnormal membranes with ruffled surfaces, abnormal expression of adhesion molecules, and loss of appropriate maturation markers.
Klf2	Embryonic lethality: Irregular shape of EryP with abnormal pseudopodia present. Reduced globin gene expression.
Klf1;Klf2	Klf1; Klf2 compound null mutant embryos show a more severe defect than either single null mutant.
Runx1	Embryonic lethality; EryP show abnormal “dimples” in their cell membranes. EryP-CFC numbers unaffected. Ter-119 expression reduced by half.
Gata1	EryP progenitors appear arrested in development and are more proliferative than wild-type progenitors.
Gata1; Gata2	Compound Gata1; Gata2 null mutant mice show a more severe EryP defect than single mutants. Primitive erythropoiesis is functionally absent. No βH1 globin gene is detectible in compound mutant embryos.
Sox6	Loss of inhibition of embryonic globin expression in EryD. Large, nucleated, embryonic globin-expressing cells present in circulation late in gestation.
Gsn (gelsolin)	Abnormal morphology and increase in circulating binucleated and βH1-expressing cells.
miR-126	EBs lacking miR-126 fail to support erythropoiesis. Function is via VCAM1+ supporting mesenchymal cells.
c-Myc	EpoR-Cre mice used to delete c-Myc in erythroid cells die at E12.5. Primitive erythroblasts show accelerated maturation presenting as orthochromatophilic erythroblasts when wild-type animals show basophilic erythroblasts. Nuclear condensation is accelerated in c-Myc null EryP.
Abc-me/Abcb10	Fail of EryP to proliferate, increased ROS and apoptosis.
Ldb1	Primitive erythropoieis absent from the E9.0 YS. No erythroid cells generated from Ldb1−/− ES cell cultures.
Fog1	EryP fail to mature and differentiate. Appear as immature megaloblastic and basophilic erythroblasts at E11.5.
Epo Receptor	Fewer EryP are present at E9.5.
Brg1	YS devoid of EryP at E9.5 due to apoptosis.
p400/Domino	EryP-CFC absent.
Mdm2	Mice lacking the p53-inhibitor Mdm2, but not Mdm4, develop apoptotic EryP and die at E13.5.
Adult hemoglobin	Deletion of both adult α- and β-globin genes leads to thalassemic EryP and embryonic lethality at E13.5.

References for each mutant mouse strain are in main body of text.